Hyperosmotic stress-dependent NF kappa B activation is regulated by reactive oxygen species and IGF-1 in cultured cardiomyocytes
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We have recently shown that hyperosmotic stress activates p65/RelB NF kappa B in cultured cardiomyocytes with dichotomic actions on caspase activation and cell death. It remains unexplored how NFKB is regulated in cultured rat cardiomyocytes exposed to hyperosmotic stress. We study here: (a) if hyperosmotic stress triggers reactive oxygen species (ROS) generation and in turn whether they regulate NFKB and (b) if insulin-like growth factor-1 (IGF-1) modulates ROS production and NF kappa B activation in hyperosmotically-stressed cardiomyocytes. The results showed that hyperosmotic stress generated ROS in cultured cardiac myocytes, in particular the hydroxyl and superoxide species, which were inhibited by N-acetylcysteine (NAC). Hyperosmotic stress-induced NFKB activation as determined by I kappa B alpha degradation and NF kappa B DNA binding. NFKB activation and procaspase-3 and -9 fragmentation were prevented by NAC and IGF-1. However, this growth factor did not decrease ROS generation induced by hyperosmotic stress, suggesting that its actions over NFKB and caspase activation may be due to modulation of events downstream of ROS generation. We conclude that hyperosmotic stress induces ROS, which in turn activates NF kappa B and caspases. IGF-1 prevents NFKB activation by a ROS-independent mechanism.